In the United States it is estimated that 60% of adults meet the clinical requirements to be considered overweight or clinically obese resulting in 300,000 deaths annually. See, Eberhardt et al., Urban and rural health chartbook. 2001, Health, United States Hyattsville (MD): NCHS. p. 296; General, The Surgeon General's call to action to prevent and decrease overweight and obesity:2001, R.M. U.S. Department Health and Human Services, Editor. 2001. In 2001, the Surgeon General of the United States issued a call to action to prevent and decrease the incidence and prevalence of individuals that are overweight or clinically obese. The Surgeon General's call to action to prevent and decrease overweight and obesity:2001, R.M. U.S. Department Health and Human Services, Editor. 2001. Interestingly, in this report there is no mention of the application or use of a pharmaceutical approach to the problem. However, there is a great deal of interest in the development of a pharmaceutical approach by both industrial and academic research institutions. The pharmaceutical approach is attractive since there is a strong likelihood of greater compliance due to the probable ease of application and use.
Epidemiological studies from around the world have demonstrated an incontrovertible correlation between mortality and obesity. The progress that has been made over the past 50 years in achieving our health goals with regard to prevention and control of infectious diseases, heart disease, diabetes and certain cancers has been largely wiped out by the growing epidemic of obesity. In 2001, approximately 25% of children and teenagers were overweight, over twice the percentage from just 20 years ago. Currently, well over 60% of adults are found to be overweight or obese, and over 300,000 deaths per year can be directly attributed to these conditions in the U.S. alone. These findings cut across all races, ages, ethnic groups and both genders, although certain groups, particularly minority and low socioeconomic groups, are clearly more prone than others. The Surgeon General's call to action to prevent and decrease overweight and obesity:2001, R.M. U.S. Department Health and Human Services, Editor. 2001.
Overweight, defined as a body mass index (BMI ranging from 25-29.9 kg/m2) and obesity (BMI>30 kg/m2), has been correlated with premature death, type 2 diabetes, heart disease, stroke, hypertension, gallbladder disease, osteoarthritis, sleep apnea, asthma, various breathing problems, certain cancers, high blood cholesterol, pregnancy complications, increased surgical risk, psychological disorders, and other pathological conditions too numerous to list. The Surgeon General's call to action to prevent and decrease overweight and obesity:2001, R.M. U.S. Department Health and Human Services, Editor. 2001; NHLBI, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults, N. NIH, Editor. 1998, HHS, PHS. p. 29-41. Obese individuals have a 50-100% increased risk of premature death from all these causes compared to persons with a BMI in the normal range (20-25 kg/m2). Even modest weight loss (5-15% of excess total body weight) reduces the risk factors for a least some of these diseases, particularly heart disease, in the short term. NHLBI, Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults, N. NIH, Editor. 1998, HHS, PHS. p. 29-41. Current evidence suggests that the effect may have long-term benefits as well. See id.; NIDDK, Study of health outcomes of weight-loss (SHOW) trial, NIDDK, Editor. 2001, National Institutes of Health, U.S.A.
The Surgeon General's 2001 call to action to prevent and decrease overweight and obesity emphasizes the obvious changes in the American lifestyle during the past several decades, with an ever-increasing reliance on sources of poor nutrition and an increased sedentary lifestyle. His principal call to action is to promote education in the schools and throughout the community to encourage healthy eating and regular, adequate exercise. At this point in the ongoing process, it seems very likely that the vast majority of U.S. citizens have at least a cursory knowledge of this important message. However, the current trend toward obesity shows no signs of abating, and, in fact, is predicted to worsen over time. Clearly, the main obstacle to overcome is the need for compliance with regard to diet and exercise according to directed guidelines by the general population, which represents a dim prospect.
It is an interesting feature of the Surgeon General's 2001 report that essentially no mention is made of pharmaceutical approaches to the prevention and cure of overweight and obesity. Obviously, this is a keen area of interest among both academic and industrial institutions, since such an approach potentially could reduce the need for patient compliance. Enormous progress has been made in recent years in understanding the roles and functions of adipose tissue (reviewed by Frayn et al., Integrative physiology of human adipose tissue. Int J Obes Relat Metab Disord, 2003. 27(8): p. 875-88), both from the standpoints of regulation of energy storage and as a secretory cell. The picture that has emerged is very complex, since it involves the activity of the autonomic nervous system, the delivery of complex mixtures of substrates and hormones, feedback from autocrine and paracrine effectors secreted by adipocytes and also vascular supply to the fat tissue. Also, factors such as leptin and adiponectin secreted by adipocytes have a general effect on general metabolism. See, Guerre-Millo, Adipose tissue hormones. J Endocrinol Invest, 2002. 25(10):855-61; Kishida, Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. Biochem Biophys Res Commun, 2003. 306(1):286-92; Miner, The adipocyte as an endocrine cell. J Anim Sci, 2004. 82(3):935-41; Rabin, et al., Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther, 2005. 3(3):465-71; Houseknecht et al., The biology of leptin: a review. J Anim Sci, 1998. 76(5):1405-20; Mantzoros, The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med, 1999. 130(8):671-80.
From this, it is clear that a very integrative, holistic approach is required to gain a full understanding of the normal and pathological states that form the basis for the current problem with overweight and obesity described above.
Many types of animals are used for research, agriculture and companionship. In some instances the costs of housing and feeding such animals is great. Smaller-sized animals would cost less to feed and house than normal sized animals. Therefore, compositions and methods of producing reduced-sized animal(s) and/or reduced weight animal(s) can be advantageous. Also, obesity in companion animals is a problem. Obesity can cause shortened lifespan and many of the same diseases and conditions mentioned above for humans.